The present invention relates to techniques for producing fused proteins useful as immunogens of therapeutic and preventive vaccines by expressing genes for fused proteins of antigens used for vaccines with lymphokines in eucaryotes or procaryotes, using recombinant DNA techniques. Further, the present invention relates to techniques for producing hybrid proteins useful as immunogens of therapeutic and preventive vaccines by chemically combining antigens used for vaccines with lymphokines.
A substance for stimulating immune responses to an antigen is called an adjuvant, which is often added to vaccines as an auxiliary substance. As the adjuvants most generally used, there are known aluminium hydroxide, aluminium phosphate and Freund's adjuvants. At present, aluminium hydroxide and aluminium phosphate are used for human, and Freund's adjuvants can not be used for human because of their strong side effects. As alternative substances to aluminium hydroxide and aluminium phosphate, there have been studied muramyldipeptide (MDP) derivatives, various lymphokines, lipid A derivatives, cholera toxins and the like.
Most of antigens produced by gene engineering technique generally have weak immunogenicity. It has therefore been desired to develop a strong adjuvant having reduced side effects in lieu of aluminium hydroxide and aluminium phosphate, or to prepare an antigen having improved immunogenicity, for the purpose of enhancing the immunogenicity of these antigens.